High resolution mapping of 3D chromatin structure

As part of a collaboration with Victor Corces’ and Job Dekker’s groups we have been working on methods for deriving sensitive high-resolution maps of 3D chromatin structure from 5C datasets. The first paper using these methods, “Architectural Protein Subclasses Shape 3D Organization of Genomes during Lineage Commitment” led by Jennifer Phillips-Cremins shows that 3D chromatin architecture changes at the sub-megabase scale during differentiation from mouse ES to NPC cells, and that CTCF, mediator, and cohesin are involved in organizing these interactions, but that different sets of proteins are involved in interactions at different length scales. Importantly, the increased resolution achieved with our 5C approach clearly shows that chromatin is organized in a hierarchical structure, with additional layers of domain organization below the level of “topological domains” as previously described.